# Renal denervation in 2025: long-term evidence supporting sympathetic modulation as a durable strategy for uncontrolled hypertension

## TL;DR

Renal denervation shows long-term effectiveness in lowering blood pressure for patients with uncontrolled hypertension.

## Contribution

New 3-year evidence confirms the durability and safety of renal denervation as a treatment for uncontrolled hypertension.

## Key findings

- SPYRAL HTN-ON MED showed a 6.8 mmHg greater SBP reduction with RDN compared to sham at 3 years.
- GSR-DEFINE registry reported a 20.5 mmHg SBP reduction at 3 years with increasing effect over time.
- RDN was associated with a 43% reduction in acute hypertensive events.

## Abstract

Renal denervation (RDN) has emerged as a promising device-based therapy for uncontrolled hypertension. Recent data from major cardiovascular conferences (EuroPCR, ESH, TCT 2025) provide unprecedented 3-year follow-up evidence on efficacy, safety, and clinical outcomes.

We synthesize key findings from the SPYRAL HTN-ON MED 3-year final report, the Global Symplicity Registry DEFINE (GSR-DEFINE) real-world data, SPYRAL AFFIRM post-approval study, and pooled analyses on acute hypertensive events. Data sources are distiguisehed by level of evidence: randomized sham-controlled trials versus observational registry data.

At 3 years, SPYRAL HTN-ON MED demonstrated sustained office systolic blood pressure (SBP) reductions of −18.5 mmHg (RDN) versus −11.7 mmHg (sham), with treatment difference of −6.8 mmHg (p = 0.0002). The GSR-DEFINE registry (n = 3109) showed −20.5 mmHg office SBP reduction at 3 years with progressively increasing effect over time. Pooled analysis revealed a 43% reduction in acute hypertensive events with RDN. No renal artery stenosis or need for reintervention was observed through 3 years.

These data support RDN as a potentially durable and safe adjunctive therapy for uncontrolled hypertension in appropriately selected patients. Benefits appear to extend to high-risk populations including patients with diabetes, chronic kidney disease, and prior stroke, though long-term cardiovascular outcome data remain awaited.